In recent years, a variety of multimodal and multifunctional nanoparticles have been developed for biomedical applications such as cellular imaging, biomolecule detection, and medical diagnosis and treatment. A common platform of multifunction nanoparticles is metallic ones with localized surface plasmon resonances. A drawback of metallic nanoparticles for biomedical applications is the Ohmic loss that leads to fluorescence quenching of attached molecules and local heating under light irradiation. We have been developing metal-free nanoprobes capable of scattering/fluorescence dual-mode imaging, medical diagnosis and photothermal therapy. The nanoprobes are composed of a silicon nanosphere core having Mie resonances in the visible to near infrared range and a fluorophore-doped silica shell [1, 2]. In this presentation, we first show scattering properties of the Mie resonant Si nanospheres. We then discuss the dark-field scattering and photoluminescence images/spectra of the core-shell nanoparticles and demonstrate that the fluorescence spectra are strongly modified by the Mie modes of a silicon nanosphere core by the Purcell effect. We demonstrate in the in vitro imaging of human cancer cells that the developed core-shell nanoparticles work as scattering/fluorescence dual-mode imaging nanoprobes.We then add the capability of glutathione sensing to the core-shell nanoprobes. It is known that the glutathione level tends to be elevated in some kinds of cancers and thus it can be used as a biomarker. To add the capability of glutathione sensing, we cover the surface of the core-shell nanoprobes with manganese oxide (MnO2). MnO2 quenches the fluorescence of the core-shell nanoparticles, and it is recovered if the MnO2 shell is resolved by the reaction with glutathione. Therefore, we can monitor the glutathione level by the fluorescence intensity. The advantage of the dual-mode imaging is that the glutathione level can be monitored by the fluorescence intensity, while the particle position is always monitored by the scattering image.Finally, we discuss the capability of Si nanospheres for photothermal therapy. We show that Si nanospheres exhibit efficient light absorption at the wavelengths of magnetic type Mie resonances such as magnetic dipole (MD) and magnetic quadrupole (MQ) resonances, and can be heated up very easily by light irradiation. An advantage of Si nanospheres compared to plasmonic nanoparticles as a light absorber for photothermal therapy is the much narrower resonances. Because of the narrow resonance, we can easily switch heating and non-heating modes. This means that if we want to heat up a nanoparticle, we can choose a specific wavelength that corresponds to e.g., the MQ mode, while if we want to excite fluorophores without heating, we can choose off-resonance wavelength for the excitation. Another advantage of Si nanospheres is the capability to monitor the temperature by Raman scattering. We show the relation between the temperature, wavelength and the size of silicon nanospheres and discuss the Mie modes suitable for the photothermal therapy application.
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